Abstract: Provided are antibodies and antigen-binding fragment thereof that bind to VSIG4. Various in vitro and in vivo methods and compositions related to antibodies. Methods include prevention and/or therapeutic treatment of cancer using an antibody or an antigen-binding fragment that binds to VSIG4.

Abstract: Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins.

Abstract: Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

Abstract: The present invention provides isolated monoclonal antibodies (e.g., humanized and human monoclonal antibodies) that bind to human Inducible T Cell COStimulator (ICOS) and exhibit therapeutically desirable functional properties, e.g., the ability to stimulate human ICOS activity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells, and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules, and pharmaceutical compositions comprising the antibodies of the invention are also provided. The antibodies of the invention can be used, for example, as an agonist to stimulate or enhance an immune response in a subject, e.g., antigen-specific T cell responses against a tumor or viral antigen. The antibodies of the invention can also be used in combination with other antibodies (e.g., PD-1, PD-L1, and/or CTLA-4 antibodies) to treat, for example, cancer.

Abstract: Provided herein are immunomodulatory proteins comprising ICOSL variants and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.

Abstract: Human antibodies, preferably recombinant human antibodies, both humanized and chimeric, which specifically bind to human OX40 are disclosed. Preferred antibodies have high affinity for OX40 receptor and activate the receptor in vitro and in vivo. The antibody can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, are useful for modulating receptor activity, e.g., in a human subject suffering from a disorder in which OX40 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies are provided, and methods of synthesizing the recombinant human antibodies, are also provided.

Abstract: The present invention relates to amino acid sequences that block the interaction between (a target on) an antigen presenting cell (APC) and (a target on) a T-cell. More particularly, the present invention relates to amino acid sequences that are directed against (as defined herein) a target on an APC (also referred to herein as “APC target”) or a target on a T-cell (also referred to herein as “T-cell target”). The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.

Abstract: Provided herein are methods of treating B7-H1-expressing tumors comprising administering an effective amount of MEDI4736 or an antigen-binding fragment thereof.

Abstract: The present invention relates to immunoglobulin single variable domain sequences that are directed against (as defined herein) OX40L, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such immunoglobulin single variable domain sequences. In particular these immunoglobulin single variable domain sequences can block binding of OX40L to OX40. The immunoglobulin single variable domains, compounds and constructs can be used for prophylactic, therapeutic or diagnostic purposes, such as for the treatment of inflammatory disease and/or disorder such as e.g. asthma, allergic asthma, chronic colitis, Crohn's disease, inflammatory bowel disease, and/or arthrosclerosis.

Abstract: A fusion protein for restoring functions of failing immune cells and application thereof. The fusion protein has a functional area for recognizing the failing immune cell and a functional area for conducting activation and amplification on the failing immune cell. The two functional areas are connected through a non-functional amino acid fragment with a certain length. The functional area for recognition uses the immune checkpoint specific antibody to recognize a phenotypic receptor of failing immune cells. The functional area for conducting activation and amplification adopts the cytokine or functionally-similar mutants, a ligand of the phenotypic receptor or functionally-similar mutants or an activating antibody to activate failing immune cells.

Abstract: The present invention provides methods and compositions for converting a T cell into a cell that exhibits at least one regulatory T cell phenotype. The converted T cell is generated by contacting a T cell with a cell that is modified to comprise an agent capable of activating PD1 signaling in a T cell. The converted T cell is useful for preventing, suppressing, blocking or inhibiting an immune response. For example the converted T cell is useful for preventing rejection of a transplanted tissue in a human or other animal host, or protecting against graft versus host disease. The converted T cell can also be used to treat autoimmune diseases.

Abstract: The present disclosure provides novel co-stimulatory domains useful in genetically-modified cells to promote cell proliferation and/or promote cytokine secretion after antigen recognition. For example, disclosed herein are genetically-modified cells comprising a chimeric antigen receptor or an inducible regulatory construct incorporating the co-stimulatory domains disclosed herein. Also disclosed herein are plasmids and viral vectors comprising a nucleic acid sequence encoding the co-stimulatory domains, and methods of administering compositions comprising the novel co-stimulatory domains to subjects in order to reduce the symptoms, progression, or occurrence of disease, such as cancer.

Abstract: The invention relates to methods of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of an inhibitor of the interaction between the PD-1 receptor and its ligand PD-L1.

Abstract: The present invention relates to a novel regulatory T cell protein. This protein, designated PD-L3 OR VISTA resembles members of the PD-L1 family, identified a novel and structurally-distinct, Ig-superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family ligand PD-L1. This molecule is designated as PD-L3 OR VISTA or V-domain Immunoglobulin Suppressor of T cell Activation (VISTA). Expression of VISTA is primarily within the hematopoietic compartment and is highly regulated on myeloid APCs and T cells. Therapeutic intervention of the VISTA inhibitory pathway represents a novel approach to modulate T cell-mediated immunity for the treatment of a wide variety of cancers, e.g., ovarian, bladder cancer and melanomas. Also, VISTA proteins, especially multimeric VISTA proteins and antibodies may be used to suppress T cell immunity in autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis and artritic conditions such as RA.

Abstract: Compositions and methods for co-expressing a secretable vaccine protein (such as gp96-Ig) and T-cell co-stimulatory molecules from a single vector, among others, are provided herein. Materials and methods for using gp96-Ig vaccination and T-cell co-stimulation to treat a clinical condition (e.g., cancer) in a subject also are provided.

Abstract: Compositions and methods for co-expressing a secretable vaccine protein (such as gp96-Ig) and T-cell co-stimulatory molecules from a single vector, among others, are provided herein. Materials and methods for using gp96-Ig vaccination and T-cell co-stimulation to treat a clinical condition (e.g., cancer) in a subject also are provided.

Abstract: The present application relates to anti-PD-L1 antibodies or antigen binding fragments thereof, nucleic acid encoding the same, therapeutic compositions thereof, and their use to enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, such as tumor immunity, for the treatment of and cancer.

Abstract: The present invention provides antibodies directed against ICOS or a derivative thereof which neutralize ICOS engagement on Treg by inhibiting the fixation between ICOS and ICOS-L and abrogate proliferation of Treg induced by plasmacytoid dendritic cells. The present invention further provides antibodies directed against ICOS or a derivative thereof which induce IL-10 and IFN? production, induce CD4? T cells proliferation, reduce Tconv proliferation, and increase the immunosuppressive function of Treg.

Abstract: The present invention relates to a fusion proteins comprising regulatory T cell protein, VISTA (V-domain Immunoglobulin Suppressor of T cell Activation (PD-L3) and an immunoglobulin protein (Ig). The invention also provides the use of VISTA polypeptides, multimeric VISTA polypeptides, VISTA-conjugates (e.g., VISTA-Ig), and VISTA antagonists for the treatment of autoimmune disease, allergy, and inflammatory conditions.

Abstract: The present invention provides antibodies that bind to the T-cell co-inhibitor programmed death-1 (PD-1) protein, and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that bind to PD-1. In certain embodiments, the present invention provides multi-specific antigen-binding molecules comprising a first binding specificity that binds to PD-1 and a second binding specificity that binds to an autoimmune tissue antigen, another T-cell co-inhibitor, an Fc receptor, or a T-cell receptor. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing PD-1 activity, thus providing a means of treating a disease or disorder such as cancer or a chronic viral infection. In other embodiments, the antibodies are useful for enhancing or stimulating PD-1 activity, thus providing a means of treating, for example, an autoimmune disease or disorder.